1,4-dioxaspiro[4.5]decan-9-one

Uses

1,4-Dioxaspiro[4,5]decan-7-one is a chemical reagent used in the preparation of rhodesain inhibitors which combat trypanosoma brucei parasites.

Synthesis

1. Cyclohexane-1,3-dione (500 g, 4.459 mol), 4A molecular sieves (500 g, 4.459 mol) and p-toluenesulfonic acid (254 g, 1.338 mol) were dissolved in anhydrous ethylene glycol (2 L) under nitrogen protection. 2. The reaction mixture was stirred at room temperature for 4 hours. 3. After completion of the reaction, the reaction mixture was adjusted to an alkaline pH with saturated NaHCO3 solution (1 L). 4. Extract the basic mixture with ethyl acetate (3 × 1 L). 5. 5. The organic phases were combined and washed with brine solution (500 mL) and subsequently dried with Na2SO4. 6. The dried organic phase was filtered and concentrated under reduced pressure to afford 1,4-dioxaspiro[4.5]decan-7-one (280 g, 1.732 mol, 38.8% yield) as a yellow liquid. 7. The product was confirmed by LCMS, m/z 157.1 (M + H+).

References

[1] Journal of Mass Spectrometry, 1998, vol. 33, # 3, p. 229 - 241
[2] Synthetic Communications, 1999, vol. 29, # 18, p. 3097 - 3106
[3] Journal of the Chemical Society - Perkin Transactions 1, 1999, # 13, p. 1885 - 1892
[4] Journal of the Chemical Society, Chemical Communications, 1993, # 4, p. 364 - 365
[5] Journal of the American Chemical Society, 1986, vol. 108, # 24, p. 7575 - 7579